Siân C Owen

Comments

Concentrated aqueous solutions are used to prepare pastilles since on drying they form solid rubbery or glasslike masses depending upon the concentration used. Foreign policy changes and politically unstable conditions in Sudan, which is the principal supplier of acacia, has created a need to find a suitable replacement.(10) Poloxamer 188 (12–15% w/w) can be used to make an oil/water emulsion with similar rheological character- istics to acacia. Other natural by-products of foods can also be used.(11) Acacia is also used in the food industry as an emulsifier, stabilizer, and thickener. A specification for acacia is contained in the Food Chemicals Codex (FCC).

The EINECS number for acacia is 232-519-5.

Specific References

Attama AA, Adiknu MV, Okoli ND. Studies on bioadhesive granules. STP Pharma Sci 2003; 13(3): 177–181.

Streubel A, Siepmann J, Bodmeier R. Floating matrix tablets based on low density foam powder. Eur J Pharm Sci 2003; 18: 37–45.

Bahardwaj TR, Kanwar M, Lai R, Gupta A. Natural gums and modified natural gums as sustained-release carriers. Drug Dev Ind Pharm 2000; 26(10): 1025–1038.

Buffo R, Reineccius G. Optimization of gum acacia/modified starch/maltodextrin blends for spray drying of flavors. Perfumer & Flavorist 2000; 25: 45–54.

Richards RME, Al Shawa R. Investigation of the effect of microwave irradiation on acacia powder. J Pharm Pharmacol 1980; 32: 45P.

Maytum CK, Magath TB. Sensitivity to acacia. J Am Med Assoc

1932; 99: 2251.

Smolinske SC. Handbook of Food, Drug, and Cosmetic Excipi- ents. Boca Raton, FL: CRC Press, 1992: 7–11.

FAO/WHO. Evaluation of certain food additives and contami- nants. Thirty-fifth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1990; No. 789.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials,

11th edn. New York: Wiley, 2004: 289.

Scheindlin S. Acacia – a remarkable excipient: the past, present, and future of gum arabic. JAMA 2001; 41(5): 669–671.

I-Achi A, Greenwood R, Akin-Isijola A. Experimenting with a new emulsifying agent (tahini) in mineral oil. Int J Pharm Compound 2000; 4(4): 315–317.

Acacia 3

General References

Anderson DMW, Dea ICM. Recent advances in the chemistry of acacia gums. J Soc Cosmet Chem 1971; 22: 61–76.

Anderson DM, Douglas DM, Morrison NA, Wang WP. Specifications for gum arabic (Acacia Senegal): analytical data for samples collected between 1904 and 1989. Food Add Contam 1990; 7:

303–321.

Aspinal GO. Gums and mucilages. Adv Carbohydr Chem Biochem

1969; 24: 333–379.

Whistler RL. Industrial Gums. New York: Academic Press, 1959.



Authors

AH Kibbe.

Date of Revision

20 August 2005.

Acesulfame Potassium

Nonproprietary Names

PhEur: Acesulfamum kalicum

Synonyms

Acesulfame K; E950; 6-methyl-3,4-dihydro-1,2,3-oxathiazin- 4(3H)-one 2,2-dioxide potassium salt; Sunett; Sweet One.

Chemical Name and CAS Registry Number

6-Methyl-1,2,3-oxathiazin-4(3H)-one-2,2-dioxide potassium salt [55589-62-3]

Empirical Formula and Molecular Weight

C4H4KNO4S   201.24

Structural Formula

 

Functional Category

Sweetening agent.

Applications in Pharmaceutical Formulation or Technology

Acesulfame potassium is used as an intense sweetening agent in cosmetics, foods, beverage products, table-top sweeteners, vitamin and pharmaceutical preparations, including powder mixes, tablets, and liquid products. It is widely used as a sugar substitute in compounded formulations,(1) and as a toothpaste sweetener.(2)

The approximate sweetening power is 180–200 times that of sucrose. It enhances flavor systems and can be used to mask some unpleasant taste characteristics.

Description

Acesulfame potassium occurs as a colorless to white-colored, odorless, crystalline powder with an intensely sweet taste.

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for acesulfame potassium.

Test PhEur 2005

Characters +

Identification +

Appearance of solution +

Acidity or alkalinity +

Acetylacetamide +

Impurity B and related substances 420 ppm

Fluorides 43 ppm

Heavy metals 45 ppm

Loss on drying 41.0%

Assay 99.0–101.0%

SEM: 1

Excipient: Acesulfame potassium

Magnification: 150×

Voltage: 5 kV

 

Typical Properties

Bonding index: 0.007

Brittle fracture index: 0.08(3)

Flowability: 19% (Carr compressibility index)(3)

Density (bulk): 1.04 g/cm3(3) Density (tapped): 1.28 g/cm3(3) Elastic modulus: 4000 MPa(3) Melting point: 2508C Solubility: see Table II.

Specific volume: 0.538 cm3/g(4) Tensile strength: 0.5 MPa(3) Viscoelastic index: 2.6(3)

Acesulfame Potassium 5

Table II: Solubility of acesulfame potassium.

Solvent Solubility at 208C unless otherwise stated

Ethanol 1 in 1000

Ethanol (50%) 1 in 100

Water 1 in 7.1 at 08C

1 in 3.7

1 in 0.77 at 1008C

Stability and Storage Conditions

Acesulfame potassium possesses good stability. In the bulk form it shows no sign of decomposition at ambient temperature over many years. In aqueous solutions (pH 3.0–3.5 at 208C) no reduction in sweetness was observed over a period of approximately 2 years. Stability at elevated temperatures is good, although some decomposition was noted following storage at 408C for several months. Sterilization and pasteur- ization do not affect the taste of acesulfame potassium.(5)

The bulk material should be stored in a well-closed container in a cool, dry place.

Incompatibilities

—

Method of Manufacture

Acesulfame potassium is synthesized from acetoacetic acid tert- butyl ester and fluorosulfonyl isocyanate. The resulting compound is transformed to fluorosulfonyl acetoacetic acid amide, which is then cyclized in the presence of potassium hydroxide to form the oxathiazinone dioxide ring system. Because of the strong acidity of this compound, the potassium salt is produced directly.

An alternative synthesis route for acesulfame potassium starts with the reaction between diketene and amidosulfonic acid. In the presence of dehydrating agents, and after neutralization with potassium hydroxide, acesulfame potas- sium is formed.

Safety

Acesulfame potassium is widely used in beverages, cosmetics, foods, and pharmaceutical formulations and is generally regarded as a relatively nontoxic and nonirritant material. Pharmacokinetic studies have shown that acesulfame potas- sium is not metabolized and is rapidly excreted unchanged in the urine. Long-term feeding studies in rats and dogs showed no evidence to suggest acesulfame potassium is mutagenic or carcinogenic.(6)

The WHO has set an acceptable daily intake for acesulfame potassium of up to 15 mg/kg body-weight.(6)

LD50 (rat, IP): 2.2 g/kg(5) LD50 (rat, oral): 6.9–8.0 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection, gloves, and a dust mask are recommended.

Regulatory Status

Included in the FDA Inactive Ingredients Guide for oral and sublingual preparations. Included in the Canadian List of



Acceptable Non-medicinal Ingredients. Accepted for use in Europe as a food additive. It is also accepted for use in certain food products in the USA and several countries in Central and South America, the Middle East, Africa, Asia, and Australia.

Related Substances

Alitame.

Comments

The perceived intensity of sweeteners relative to sucrose depends upon their concentration, temperature of tasting, and pH, and on the flavor and texture of the product concerned.

Intense sweetening agents will not replace the bulk, textural, or preservative characteristics of sugar, if sugar is removed from a formulation.

Synergistic effects for combinations of sweeteners have been reported, e.g., acesulfame potassium with aspartame or sodium cyclamate. A ternary combination of sweeteners that includes acesulfame potassium and sodium saccharin has a greater decrease in sweetness upon repeated tasting than other combinations.(7)

Note that free acesulfame acid is not suitable for use as a sweetener.

A specification for acesulfame potassium is contained in the Food Chemicals Codex (FCC).

Specific References

Kloesel L. Sugar substitutes. Int J Pharm Compound 2000; 4(2): 86–87.

Schmidt R, Janssen E, Haussler O, et al. Evaluating toothpaste sweetening. Cosmet Toilet 2000; 115: 49–53.

Mullarney MP, Hancock BC, Carlson GT, Ladipo DD. The powder flow and compact mechanical properties of sucrose and three high-intensity sweeteners used in chewable tablets. Int J Pharm 2003; 257: 227–236.

Birch GG, Haywood KA, Hanniffy GG, et al. Apparent specific volumes and tastes of cyclamates, other sulfamates, saccharins and acesulfame sweeteners. Food Chemistry 2004; 84: 429–435.

Lipinski G-WvR, Huddart BE. Acesulfame K. Chem Ind 1983; 11:

427–432.

FAO/WHO. Evaluation of certain food additives and contami- nants. Thirty-seventh report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1991; No. 806.

Schiffman SS, Sattely-Miller EA, Graham BG, et al. Effect of repeated presentation on sweetness intensity of binary and tertiary mixtures of sweetness. Chem Senses 2003; 28: 219–229.

General References

Anonymous. Artificial sweetners. Can Pharm J 1996; 129: 22.

Lipinski G-WvR, Lu¨ ck E. Acesulfame K: a new sweetener for oral cosmetics. Manuf Chem 1981; 52(5): 37.

Marie S. Sweeteners. In: Smith J, ed. Food Additives User’s Handbook.

Glasgow: Blackie, 1991: 47–74.

Nutrinova. Technical literature: Sunett in Pharmaceuticals, 1998.

Authors

JH Chu.

Date of Revision

12 August 2005.

Acetic Acid, Glacial

Nonproprietary Names

BP: Glacial acetic acid JP: Glacial acetic acid

PhEur: Acidum aceticum glaciale USP: Glacial acetic acid

Synonyms

E260; ethanoic acid; ethylic acid; methane carboxylic acid; vinegar acid.

Table I: Pharmacopeial specifications for glacial acetic acid.

Test JP 2001 PhEur 2005 USP 28

Identification + + +

Characters + + — Freezing point 514.58C 514.88C 515.68C Nonvolatile matter 41.0 mg 40.01% 41.0 mg Sulfate + + +

Chloride + + +

Heavy metals 410 ppm  45 ppm 45 ppm

Iron — 45 ppm —

See also Sections 17 and 18.

Readily oxidizable

impurities

+ + +

Chemical Name and CAS Registry Number

Ethanolic acid [64-19-7]

Empirical Formula and Molecular Weight

C2H4O2 60.05

Structural Formula

 

Functional Category

Acidifying agent.

Applications in Pharmaceutical Formulations or Technology

Glacial and diluted acetic acid solutions are widely used as acidifying agents in a variety of pharmaceutical formulations and food preparations. Acetic acid is used in pharmaceutical products as a buffer system when combined with an acetate salt such as sodium acetate. Acetic acid is also claimed to have some antibacterial and antifungal properties.

Description

Glacial acetic acid occurs as a crystalline mass or a clear, colorless volatile solution with a pungent odor.

Pharmacopeial Specifications

See Table I.

Assay 599.0% 99.5–100.5%  99.5–100.5%